Among the many hundred known processes for alcohol oxidation, comparatively few metal-catalyzed examples have been developed. One notable exception has been the use of catalytic palladium(II) systems, which often provide efficient oxidation of sec-alcohols to ketones in high yield (Blackburn et al., J. Chem. Soc., Chem. Commun. 157 (1977); Tamaru et al., Tetrahedron Lett. 20:1401 (1979); Nagashima et al., Chem. Lett. 1171 (1981); Aït-Mohand et al., Tetrahedron Lett. 36:2473 (1995); Peterson et al, J. Org. Chem. 63:3185 (1998); Nishimura et al., J. Org. Chem. 64:6750 (1999); and ten Brink et al., Science 287:1636 (2000)). Interestingly, palladium(II) oxidations have been successfully implemented using a wide variety of co-oxidants, including allyl carbonates, aryl halides, CCl4, and molecular oxygen. The kinetic resolution of sec-alcohols has been studied in a number of systems that utilize chiral ligands. The exploratory studies that focused on chiral phosphine ligands in the presence of organic oxidants established that modest levels of asymmetric induction were attainable under a range of conditions. However, these studies also showed that reactions carried out under these conditions were plagued by a variety of side reactions and inconsistencies.
Therefore, the oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxylation, and aziridination, it is surprising that there are relatively few catalytic enantioselective examples of the ubiquitous alcohol oxidation.
Accordingly, there is a continuing need in the art for improved enantioselective oxidation methods, as well as improved methods of selectively oxidizing one isomer of a racemic mixture of compounds. Additionally, there is a need in the art for catalyst systems that are useful in such methods. The present invention addresses those needs.